It is well documented that the ability of HIV to rapidly evolve drug resistance, together with toxicity problems requires the development of additional classes of antiviral drugs: AICA-riboside [a) P. D. Cook, R. K. Robins, J. Am. Chem. Soc. 1976, 78, 1492; b) A. Yamazaki, M. Okutsu, J. Heteroclycl. Chem. 1978, 15, 3353; c) T. Kalman, D.Houston, Nucleosides & Nucleotides 1989, 8, 899; d) M. Wall, S. J. Benkovic, J.Med.Chem., 1999, 42, 3421] (1-(-D-ribofuranosyl)-5-amino-4-imidazolecarboxamide) is an example of an open ring purine nucleoside showing potent antiviral activity. EICAR [A. Matsuda, T. Sasaki, T. Ueda, Chem. Pharm. Bull. 1988, 36, 2730] (5-alkynyl-1-D-ribof u ranosylimidazole-4-carboxamide), likewise an imidazole derivative, shows a strong antileukemia activity. Also a bicyclic imidazole containing non-nucleoside derivative [E. J. Saloski, Tetrahedron Lett. 1995, 36, 1387] is reported as a HIV-1 reverse transcriptase inhibitor.
Many non nucleoside derivatives have been reported to inhibit proliferation of HIV and especially non-nucleoside reverse transcriptase inhibitors (NNRTI) make up a large part of these compounds. Excellent reviews describing these NNRTI can be found [a) M. Witvrouw et al., AIDS, 1999, 13, 1477–1483; b) E. De Clercq, Il Farmaco 1999, 54, 26–45]. A few N-aminoimidazolethione derivatives have been reported before and were obtained by a multistep reaction from α-halo-ketones, potassium thiocyanate and monosubstituted hydrazines [J. G. Schantl, I. M. Lagoja, Heterocycles, 1997, 45, 691].
However, there is still a need for compounds which either complement existing drugs such that the resulting cocktail has improved resistance to virus mutation or compounds which are themselves effective against many or all viable mutations of a virus.